Is WT1 p.Gln214Pro (c.641A>C) pathogenic?

WT1 p.Gln214Pro (c.641A>C) is classified Uncertain significance in WT1 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2024-12-20). Very rare (popmax 0.00133%, afr); Associated with Wilms tumor 1.

What condition is associated with WT1 p.Gln214Pro (c.641A>C)?

WT1 p.Gln214Pro (c.641A>C) is associated with Wilms tumor 1, malignant mesothelioma, Frasier syndrome (ClinVar).

How common is WT1 p.Gln214Pro (c.641A>C) in the general population?

WT1 p.Gln214Pro (c.641A>C) is very rare (popmax 0.00133%, afr) (gnomAD).

WT1 p.Gln214Pro

c.641A>C · rs771024882 · VCV577219

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Conditions

Wilms tumor 1

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.275	benign-leaning
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 6	GERP 1.6, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 39 kb · p 0.077 · regional, not allelic
Overall
CADD	23.2	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00133% African / African-American · 1/74,942 alleles

Filtering AF 0.000615% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000474%

Overall 0.00093% 15/1,612,878 alleles · very rare exomes 14/1,460,650 · genomes 1/152,228 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0016%	62,466
African / African-Americangrpmax	0.00133%	74,942
European (non-Finnish)	0.0011%	90,766

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: WT1
Protein: p.Gln214Pro
Coding: c.641A>C
MANE Select: NM_024426
dbSNP: rs771024882
Type: single nucleotide variant
Location: chr11:32434720 (GRCh38)

Full WT1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Wilms tumor 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: malignant mesothelioma Frasier syndrome WAGR syndrome Denys-Drash syndrome nephrotic syndrome, type 4 Meacham syndrome

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/wt1-p-gln214pro (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown